I propose to apply methods of theoretical conformational analysis to the study of the conformation of the collagen molecule and of its packing in fibrils, both in the normal state and when its structure is altered, as a result of aging processes or of connective tissue diseases such as elastosis and rheumatic fever. Conformational energy computations will be used to analyze the effect of amino acid substitutions on the exact conformation of the triple helix and on the packing and longitudinal alignment of triple helices. New methods of accounting for solvent interactions in the expressions for the conformational free energy will be tested on collagen. The computational procedures will be applied also to the non-helical N-terminal peptide of collagen. Since this region of the molecule is essential in cross-linking, its study will contribute to the elucidation of correlations between cross-linking and molecular rearrangements. At the same time, this peptide provides some advantages in the testing of theories for the computation of protein folding. Relationships to be developed between conformational and packing stability on one hand and covalent cross-linking on the other hand will aid the understanding of physico-chemical and physiological events in the functioning of normal and of pathologically modified collagen.